PMID- 35242275
OWN - NLM
STAT- MEDLINE
DCOM- 20220324
LR  - 20220324
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2022
DP  - 2022
TI  - Diet-Induced High Serum Levels of Trimethylamine-N-oxide Enhance the Cellular 
      Inflammatory Response without Exacerbating Acute Intracerebral Hemorrhage Injury 
      in Mice.
PG  - 1599747
LID - 10.1155/2022/1599747 [doi]
LID - 1599747
AB  - Trimethylamine-N-oxide (TMAO), an intestinal flora metabolite of choline, may 
      aggravate atherosclerosis by inducing a chronic inflammatory response and thereby 
      promoting the occurrence of cerebrovascular diseases. Knowledge about the 
      influence of TMAO-related inflammatory response on the pathological process of 
      acute stroke is limited. This study was designed to explore the effects of TMAO 
      on neuroinflammation, brain injury severity, and long-term neurologic function in 
      mice with acute intracerebral hemorrhage (ICH). We fed mice with either a regular 
      chow diet or a chow diet supplemented with 1.2% choline pre- and post-ICH. In 
      this study, we measured serum levels of TMAO with ultrahigh-performance liquid 
      chromatography-tandem mass spectrometry at 24 h and 72 h post-ICH. The expression 
      level of P38-mitogen-protein kinase (P38-MAPK), myeloid differentiation factor 88 
      (MyD88), high-mobility group box1 protein (HMGB1), and interleukin-1beta (IL-1beta) 
      around hematoma was examined by western blotting at 24 h. Microglial and 
      astrocyte activation and neutrophil infiltration were examined at 72 h. The 
      lesion was examined on days 3 and 28. Neurologic deficits were examined for 28 
      days. A long-term choline diet significantly increased serum levels of TMAO 
      compared with a regular diet at 24 h and 72 h after sham operation or ICH. 
      Choline diet-induced high serum levels of TMAO did not enhance the expression of 
      P38-MAPK, MyD88, HMGB1, or IL-1beta at 24 h. However, it did increase the number of 
      activated microglia and astrocytes around the hematoma at 72 h. Contrary to our 
      expectations, it did not aggravate acute or long-term histologic damage or 
      neurologic deficits after ICH. In summary, choline diet-induced high serum levels 
      of TMAO increased the cellular inflammatory response probably by activating 
      microglia and astrocytes. However, it did not aggravate brain injury or worsen 
      long-term neurologic deficits. Although TMAO might be a potential risk factor for 
      cerebrovascular diseases, this exploratory study did not support that TMAO is a 
      promising target for ICH therapy.
CI  - Copyright (c) 2022 Caizhen Li et al.
FAU - Li, Caizhen
AU  - Li C
AUID- ORCID: 0000-0001-6854-116X
AD  - Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Zhu, Li
AU  - Zhu L
AD  - Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Dai, Yinming
AU  - Dai Y
AD  - Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Zhang, Zhiying
AU  - Zhang Z
AD  - Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Huang, Leo
AU  - Huang L
AD  - Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
FAU - Wang, Tom J
AU  - Wang TJ
AD  - Winston Churchill High School, Potomac, Maryland, USA.
FAU - Fu, Peiji
AU  - Fu P
AD  - Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Li, Yinuo
AU  - Li Y
AD  - Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Wang, Jian
AU  - Wang J
AUID- ORCID: 0000-0003-2291-640X
AD  - Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
AD  - Department of Anatomy, College of Basic Medical Sciences, Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Jiang, Chao
AU  - Jiang C
AUID- ORCID: 0000-0001-5588-4294
AD  - Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
LA  - eng
PT  - Journal Article
DEP - 20220216
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Methylamines)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - FLD0K1SJ1A (trimethyloxamine)
RN  - N91BDP6H0X (Choline)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Brain Injuries/*blood/*complications/microbiology
MH  - Cerebral Hemorrhage/*blood/*complications/microbiology
MH  - Choline/*adverse effects
MH  - Diet/*adverse effects
MH  - Disease Models, Animal
MH  - Gastrointestinal Microbiome
MH  - Inflammation/blood/chemically induced
MH  - Interleukin-1beta/metabolism
MH  - Male
MH  - Methylamines/*blood
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/*metabolism
MH  - Neutrophil Infiltration/drug effects
MH  - Neutrophils/immunology
MH  - Signal Transduction/*drug effects
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC8886754
COIS- The authors declare that they have no competing interests.
EDAT- 2022/03/05 06:00
MHDA- 2022/03/25 06:00
PMCR- 2022/02/16
CRDT- 2022/03/04 05:40
PHST- 2021/09/28 00:00 [received]
PHST- 2022/01/27 00:00 [accepted]
PHST- 2022/03/04 05:40 [entrez]
PHST- 2022/03/05 06:00 [pubmed]
PHST- 2022/03/25 06:00 [medline]
PHST- 2022/02/16 00:00 [pmc-release]
AID - 10.1155/2022/1599747 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2022 Feb 16;2022:1599747. doi: 10.1155/2022/1599747. 
      eCollection 2022.